Wound healing is a complex dynamic process that results in the restoration of anatomic continuity and function; an ideally healed wound is one that has returned to normal anatomic structure, function and appearance. The classic model of wound healing is divided into three or four sequential, yet overlapping, phases: (1) the immediate response, (2) the inflammatory response, (3) proliferation of wound-edge epithelium and (4) tissue regeneration (remodeling). During the inflammation phase, platelet aggregation and clotting from a matrix which traps the plasma proteins and blood cells to induce the influx of various types of cells. During the cellular proliferation phase, new connective or granulation tissue and blood vessels are formed. During the remodeling phase, granulation tissue is replaced by a network of collagen and elastin fibers leading to the formation of scar tissue.
During human skin wound healing, a critical rate-limiting step is the initiation of the resident epidermal and dermal cells at the wound edge to migrate into the wound bed. The formation of granulation tissue in an open wound allows the reepithelialization phase to take place, as epithelial cells migrate across the new tissue to form a barrier between the wound and the environment. Basal keratinocytes from the wound edges and dermal appendages such as hair follicles, sweat glands and sebacious (oil) glands are the main cells responsible for the epithelialization phase of wound healing. They advance in a sheet across the wound site and proliferate at its edges, ceasing movement when they meet in the middle. Human keratinocytes (HKCs) laterally migrate across the wound bed from the cut edge to eventually close the wound, the process known as re-epithelialization. The dermal cells, including dermal fibroblasts (DFs) and dermal microvascular endothelial cells (HDMECs), start to move into the wound following the HKC migration, where these cells deposit matrix proteins, contract and remodel the newly closed wound and build new blood vessels. Fibroblast cells, located in the dermal layer, play important roles in wound healing by, for example, producing components of the extracellular matrix like collagen and various cytokines, which, in turn, enhance the proliferation and migration of keratinocytes.
A number of composition and methods for wound healing were developed. U.S. Pat. No. 6,232,341 provides a topical pharmaceutical composition for wound healing comprising borneol and bismuth subgallate. U.S. Pat. No. 7,888,319 discloses compositions and methods for promoting wound healing and tissue regeneration, comprising an isolated polypeptide comprising a carboxy-terminal amino acid sequence of an alpha Connexin, or a conservative variant thereof. U.S. Pat. No. 8,084,491 discloses methods of promoting wound healing comprising the administration of a therapeutically effective amount of a composition comprising topiramate. U.S. Pat. No. 8,258,093 provides a pharmaceutical composition comprising a keratin derivative (e.g., keratose, kerateine, or a combination thereof).
Lingzhi (a species of Basidiomycetes) is an herbal mushroom, used in traditional Chinese medicine for at least 2,000 years. The lingzhi mushroom or reishi mushroom encompasses several fungal species of the genus Ganoderma, and most commonly refers to the closely related species, Ganoderma lucidum and Ganoderma tsugae. Many therapeutic effects have been reported of Lingzhi species, such as immunomodulatory, anti-tumor, hepato-protective, antioxidant, and cholesterol-lowering effects. A new glycoprotein class in Lingzhi named fungal immunomodulatory proteins (FIPs) was recently identified. So far, several FIPs have been isolated and purified, including LZ-8 (from Ganoderma lucidum), FIP-fve (from Flammulina veltipes), FIP-vvo (from Volvariella volvacea), FIP-gts (from Ganoderma tsugae), and FIP-gja (from Ganoderma sinensis). According to a previous study, FIP-gts from G. tsugae, a popular chemopreventive mushroom in Asia, has anti-cancer function and is involved in the regulation of hTERT/telomerase expression (Liao et al., 2006, Mol Carcinog, 45, 220-229). US 20100009915 provides a method for suppressing proliferation of a cancer cell and a method for suppressing a tumor cell mobility, comprising providing to the tumor cell a purified polypeptide of a fungal immunomodulatory protein, LZ-8. U.S. Pat. No. 7,601,808 discloses an immunomodulatory protein (GMI) cloned from Ganoderma microsporum and this protein has immunomodulator efficiency.
However, none of prior art discloses or suggests the relationship of Lingzhi immunomodulatory protein to wound healing.